The v-sis transforming gene and its human homologue, c-sis, contain coding sequences for protein-derived growth factor-2 (PDGF-2), a major polypeptide chain of human PDGF. The primary v-sis gene product, p28sis, has been shown to be the precursor of a smaller molecule corresponding in size as well as amino acid sequence to a PDGF-2 monomer. Moreover, p28sis undergoes dimer formation and subsequent processing to a form analogous in structure to that of biologically active human PDGF. Thus, it seems likely that the transforming activity of the v-sis gene product is mediated by this processed PDGF-2-like dimer. Our present findings establish that derepression of the coding sequence for a normal human growth factor can cause it to acquire transforming properties in an appropriate target cell. Moreover, when incorporated by a retrovirus, the v-sis/PDGF-2 transforming gene has been shown to play an important role in the experimental induction of fibrosarcomas and glioblastomas. Many human glioblastomas and fibrosarcomas express sis/PDGF-2 transcripts, whereas normal fibroblasts and glial cells so far analyzed do not. Thus, the transcriptional activation of this gene may be involved in the neoplastic process leading to tumors of connective tissue origin.